Description: (Applicant's Description) Tumor cell invasion and metastasis are complex processes that may be regulated by adhesion receptors, proteinases, extracellular matrix proteins, and cytokines. Program A.4 was organized four years ago to coalesce a group of investigators working on systems and processes that are likely to be critical in tumor invasion and metastasis. The core of the program includes investigators with expertise regarding integrin structure and function, the ADAM family of adhesion/disintegrin proteins, and extracellular proteinases that have been implicated in cancer cell adhesion, motility, invasion and metastasis. During the past grant period we have begun to involve scientists studying vascular smooth muscle growth and differentiation, whose expertise is important in understanding the fundamental events in angiogenesis. Our strategy for development of Program A4 is to expand its scope and include a greater emphasis on interactions between malignant and non-malignant cells that may influence angiogenesis as well as cancer progression, migration, invasion and metastasis.